Encoding specificity theory predicts most effective recall by the original conditions at encoding, while generalization endows recall flexibly under circumstances which deviate from the originals. The CA1 regions have been implicated in memory and generalization but whether and which locally separated mechanisms are involved is not clear. We report here that fear memory is quickly formed, but generalization develops gradually over 24 h. Generalization but not fear memory is impaired by inhibiting ipsilateral (ips) or contralateral (con) CA1, and by optogenetic silencing of the ipsCA1 projections onto conCA1. By contrast, in vivo fEPSP recordings reveal that ipsCA1-conCA1 synaptic efficacy is increased with delay over 24 h when generalization is formed but it is unchanged if generalization is disrupted. Direct excitation of ipsCA1-conCA1 synapses using chemogenetic hM3Dq facilitates generalization formation. Thus, rapid generalization is an active process dependent on bilateral CA1 regions, and encoded by gradual synaptic learning in ipsCA1-conCA1 circuit.
Bibliographical noteFunding Information:
Research was supported by 973 Program of the Ministry of Science and Technology of China (2013CB835100 and 2015CB553502 to L.X.), Strategic Priority Research Program of Chinese Academy of Sciences (XDB02020002 to L.X.) and External Cooperation Program BIC of Chinese Academy of Sciences (GJHZ1549 to G.R.-L.), Youth Innovation Promotion Association of Chinese Academy of Sciences (2013250 to Q.-X.Z.), National Science Foundation of China (31100775 and 31371141 to Q.-X.Z., 8157332 to Y.-Q.D., and U1502221 to L.X.), and Science and Technology Program of Yunnan Province (2013GA003 to L.X.). We thank Mr. Jin-Yang Liu and Ms. Jia-Lin Mi for assisting chemogenetic and slow generalization study, and Mr. Jin-Yang Liu and Ms. Ni-Ya Wang for assisting c-fos staining. We thank Dr. Mu-Ming Poo for suggesting the design of single-foot fear conditioning.
© 2017 The Author(s).
ASJC Scopus subject areas
- Chemistry (all)
- Biochemistry, Genetics and Molecular Biology (all)
- Physics and Astronomy (all)